C/EBPα mediates the maturation and antitumor functions of macrophages in human hepatocellular carcinoma
Copyright © 2024 Elsevier B.V. All rights reserved..
Recent studies have suggested that therapeutic upregulation of CCAAT/enhancer binding protein α (C/EBPα) prevents hepatocellular carcinoma (HCC) progression. However, the mechanisms underlying this outcome are not fully understood. In this study, we investigated the expression and functional roles of C/EBPα in human HCC, with a focus on monocytes/macrophages (Mφs). Paraffin-embedded tissues were used to visualize C/EBPα expression and analyze the prognostic value of C/EBPα+ monocytes/Mφs in HCC patients. The underlying regulatory mechanisms were examined using human monocyte-derived Mφs. The results showed that the expression of C/EBPα on monocytes/Mφs was significantly decreased in intra-tumor tissues compared to the corresponding peri-tumor tissues. C/EBPα+ monocytes/Mφs displayed well-differentiation and antitumor capacities, and the accumulation of these cells in tissue was associated with antitumor immune responses and predicted longer overall survival (OS) of HCC patients. Mechanistic studies demonstrated that C/EBPα was required for Mφ maturation and HLA-DR, CD169 and CD86 expression, which initiates antitumor cytotoxic T-cell responses; however, these effects were inhibited by monocyte autocrine IL-6- and IL-1β-induced suppression of mTOR1 signaling. Reprogramming Mφs via the upregulation of C/EBPα may provide a novel strategy for cancer immunotherapy in patients with HCC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:585 |
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| Enthalten in: |
Cancer letters - 585(2024) vom: 31. März, Seite 216638 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Yongchun [VerfasserIn] |
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| Links: |
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| Themen: |
C/EBPα |
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| Anmerkungen: |
Date Completed 05.03.2024 Date Revised 05.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.canlet.2024.216638 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367572273 |
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| 520 | |a Recent studies have suggested that therapeutic upregulation of CCAAT/enhancer binding protein α (C/EBPα) prevents hepatocellular carcinoma (HCC) progression. However, the mechanisms underlying this outcome are not fully understood. In this study, we investigated the expression and functional roles of C/EBPα in human HCC, with a focus on monocytes/macrophages (Mφs). Paraffin-embedded tissues were used to visualize C/EBPα expression and analyze the prognostic value of C/EBPα+ monocytes/Mφs in HCC patients. The underlying regulatory mechanisms were examined using human monocyte-derived Mφs. The results showed that the expression of C/EBPα on monocytes/Mφs was significantly decreased in intra-tumor tissues compared to the corresponding peri-tumor tissues. C/EBPα+ monocytes/Mφs displayed well-differentiation and antitumor capacities, and the accumulation of these cells in tissue was associated with antitumor immune responses and predicted longer overall survival (OS) of HCC patients. Mechanistic studies demonstrated that C/EBPα was required for Mφ maturation and HLA-DR, CD169 and CD86 expression, which initiates antitumor cytotoxic T-cell responses; however, these effects were inhibited by monocyte autocrine IL-6- and IL-1β-induced suppression of mTOR1 signaling. Reprogramming Mφs via the upregulation of C/EBPα may provide a novel strategy for cancer immunotherapy in patients with HCC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a C/EBPα | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Macrophage maturation | |
| 650 | 4 | |a Prognosis | |
| 650 | 4 | |a mTOR1 | |
| 650 | 7 | |a CCAAT-Enhancer-Binding Protein-alpha |2 NLM | |
| 700 | 1 | |a Li, Zhixiong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Weibai |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Junfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Zhijie |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Xing-Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yao-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Limin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jing |e verfasserin |4 aut | |
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